Genetic severity markers in multiple sclerosis

Abstract

The present invention relates to the use of SNPs in predicting susceptibility and/or severity of Multiple Sclerosis in an individual. The SNPs are located in the introns of the glycosylation enzymes MGAT5 and XYLT1, 3′ of HIF1AN, within introns of MEGF11. FGF14, PDE9A and CDH13 and within desert regions of 4q34 and 17p13.

1 - 15 . (canceled) 
     
     
         16 . A method for genotyping comprising the steps of:
 a) using a nucleic acid isolated from a sample of an individual; and   b) determining the type of nucleotide in SNP rs3814022, rs4953911, rs2059283, rs12927173, rs2495725, rs1343522, rs4573623, rs333548, rs10508075, rs2839580, rs2495725, rs3814022, rs1078922, and/or rs4315313, in one or both alleles of the diallelic marker, and/or in SNPs in Linkage Disequilibrium (LD) with one or more of these SNPs.   
     
     
         17 . The method according to  claim 16 , wherein the identity of the nucleotides at said diallelic markers is determined for both copies of said diallelic markers present in said individual's genome. 
     
     
         18 . The method according to  claim 16 , wherein said determining is performed by a microsequencing assay. 
     
     
         19 . The method according to  claim 16 , further comprising amplifying a portion of a sequence comprising the diallelic marker prior to said determining step. 
     
     
         20 . The method according to  claim 19 . wherein said amplifying is performed by PCR. 
     
     
         21 . The method according to  claim 16 , further comprising the step of correlating the result of the genotyping steps with the severity of the disease Multiple Sclerosis. 
     
     
         22 . The method according to  claim 16 , wherein the presence of a Gin rs3814022, a T in rs4953911, an A in rs2059283, an A in rs12927173, an A in rs2495725, a G in rs1343522, a G in rs4573623, a Tin rs333548, a G in rs10508075, an A in rs2839580, an A in rs2495725, a G in rs3814022, a G in rs1078922, and/or a C in rs4315313 indicates the severity of the disease Multiple Sclerosis in said individual. 
     
     
         23 . The method according to  claim 16 , wherein the SNPs in Linkage Disequilibrium (LD) with one or more of the SNPs are characterized by a LD correlation coefficient r 2  greater than 0.8 in at least one population of at least 100 individuals. 
     
     
         24 . A composition comprising one or more SNPs selected from the group consisting of rs3814022, rs4953911, rs2059283, rs12927173, rs2495725, rs1343522, rs4573623, rs333548, rs10508075, rs2839580, rs2495725, rs3814022, rs1078922, rs4315313, or SNPs in Linkage Disequilibrium (LD) with one or more of these SNPs. 
     
     
         25 . A method which is indicative of the severity of the disease Multiple Sclerosis in an individual comprising:
 a) using the nucleic acid from a sample of said individual;   b) identifying the presence of a useful genetic marker in said individual by known methods; and   c) based on the results of step b) making a prediction of the severity of the disease Multiple Sclerosis of said individual.   
     
     
         26 . The method according to  claim 25 , wherein the genetic marker is one or more SNPs selected from the group consisting of rs3814022, rs4953911, rs2059283, rs12927173, rs2495725, rs1343522, rs4573623, rs333548, rs10508075, rs2839580, rs2495725, rs3814022, rs1078922, rs4315313, or SNPs in Linkage Disequilibrium (LD) with one or more of these SNPs. 
     
     
         27 . The method according to  claim 25  wherein the SNPs in Linkage Disequilibrium (LD) with one or more of the SNPs are characterized by a LD correlation coefficient r 2  greater than 0.8 in at least one population of at least 100 individuals. 
     
     
         28 . A method for treating Multiple Sclerosis in an individual in need thereof, the method comprising the steps:
 a) applying a method according to  claim 16 ;   b) treating said individual with an interferon-beta which individual has been identified as exhibiting one or more of the markers and wherein the severity of Multiple Sclerosis in said individual has been determined.   
     
     
         29 . The method according to  claim 28 , wherein the interferon-beta is interferon-beta 1a or 1b.